Open Access
Reduced autonomic function in patients with long-COVID-19 syndrome is mediated by cardiorespiratory fitness
(Elsevier, 2024-07-01) Oscoz Ochandorena, Sergio; Legarra Gorgoñón, Gaizka; García Alonso, Yesenia; García Alonso, Nora; Izquierdo Redín, Mikel; Ramírez Vélez, Robinson; Ciencias de la Salud; Osasun Zientziak; Ciencias humanas y de la educación; Giza eta Hezkuntza Zientziak
Background: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity¿mediated disruption of the ANS resulting particularly in exercise intolerance. Methods: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant. Results: The HRV parameters¿RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2¿were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients. CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients.
Embargo
Exercise training in long COVID: the EXER-COVID trial
(Oxford University Press, 2024-11-22) Ramírez Vélez, Robinson; Oteiza Olaso, Julio; Legarra Gorgoñón, Gaizka; Oscoz Ochandorena, Sergio; García Alonso, Nora; García Alonso, Yesenia; Correa Rodríguez, María; Soto-Mota, Adrian; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Ciencias humanas y de la educación; Giza eta Hezkuntza Zientziak
Background: the post-COVID-19 condition is a novel condition for which guidelines recommend supervised exercise, but evidence guiding safe and effective interventions is limited. The aim of this study was to investigate the effects of a tailored exercise program (EXER-COVID 5 trial) on cardiorespiratory fitness, muscle strength, long COVID symptoms, cognitive performance, quality of life, depression, and psychological distress. Methods: this crossover study included 100 participants with post-COVID-19 conditions (mean 8 age 48 years; 68% women) at a single center in Spain from March 1, 2021, to September 30, 2022. Participants were randomized 1:1 to 6 weeks of muscle power resistance training (PRT) followed by 6 weeks of usual care (Group 1 [AB], n=50) or 6 weeks of usual care followed by 6 weeks of muscle power RT (Group 2 [BA], n=50). Results: the intervention significantly improved the peak VO2 by 2.10 mL/kg/min [95% CI 1.25 to 2.94], P<0.001. Per-protocol analyses revealed similar results (2.40 mL/kg/min [95% CI 1.56 to 3.25]), P<0.001. No carry-over or period effects were detected. After power PRT, strength (1RM) was improved for pectoral press, bilateral leg-press, knee extension, and back press (P<0.001). Significant decreases were found in psychological distress scores (P<0.001). The intervention also improved quality of life (P=0.041), cognitive capabilities (P=0.014) and cognitive performance (P=0.036). Furthermore, the exercise program reduced seven of the 22 long-COVID symptoms, including weakness (RR= 0.75) dyspnea (RR= 0.56), hearing loss/tinnitus (RR= 0.86), change in appetite (RR= 0.84), memory loss (RR= 0.84), stress (RR= 0.80) and apathy/depression (RR= 0.80), (all Ps<0.05). Conclusions: a supervised 6-week PRT intervention program safely improved cardiorespiratory fitness, strength, and mental health in participants with post-COVID-19 conditions. These findings provide clinicians with evidence to support exercise as standard co-therapy and warrant further study.
Open Access
Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis.
(Elsevier, 2023) Ramírez Vélez, Robinson; Oscoz Ochandorena, Sergio; García Alonso, Yesenia; García Alonso, Nora; Legarra Gorgoñón, Gaizka; Oteiza Olaso, Julio; Ernaga Lorea, Ander; Izquierdo Redín, Mikel; Correa Rodríguez, María; Ciencias de la Salud; Osasun Zientziak
Background & aims: Long COVID syndrome (LCS) involves persistent symptoms experienced by many patients after recovering from coronavirus disease 2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism, which is closely related to substrate oxidation rates during exercise, in patients with LCS compared with healthy controls. We also examined whether muscle power output mediates the relationship between COVID-19 and skeletal muscle energy metabolism. Methods: In this cross-sectional study, we enrolled 71 patients with LCS and 63 healthy controls. We assessed clinical characteristics such as body composition, physical activity, and muscle strength. We used cardiopulmonary exercise testing to evaluate substrate oxidation rates during graded exercise. We performed statistical analyses to compare group characteristics and peak fat oxidation differences based on power output. Results: The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (V__O2) at maximum fat oxidation (g min1 ) than the healthy controls (P < 0.05). Moderation analysis indicated that muscle power output significantly influenced the relationship between LCS and reduced peak fat oxidation (interaction b ¼ 0.105 [95% confidence interval 0.174; 0.036]; P ¼ 0.026). Therefore, when muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study sample P ¼ 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy controls. Conclusion: The patients with LCS had lower peak fat oxidation during exercise compared with the healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional research should continue investigating LCS pathogenesis and the functional role of mitochondria.
Open Access
Resistance training and clinical status in patients with postdischarge symptoms after COVID-19: protocol for a randomized controlled crossover trial 'The EXER-COVID Crossover Study'.
(BMC, 2022) Ramírez Vélez, Robinson; Oteiza Olaso, Julio; Casas Fernández de Tejerina, Juan Manuel; García Alonso, Nora; Legarra Gorgoñón, Gaizka; Oscoz Ochandorena, Sergio; Arasanz Esteban, Hugo; García Alonso, Yesenia; Correa Rodríguez, María; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Background: physical exercise induces a coordinated response of multiple organ systems, including the immune system. In fact, it has been proposed that physical exercise may modulate the immune system. However, the potential effect of an exercise program on COVID-19 survivors has not been investigated. Thus, the aim of this study is to evaluate the modifications in immunological parameters, physical condition, inflammatory profile, and perceived persistent symptoms after 6 weeks of supervised resistance training (RT), in addition to the standard care on the clinical status of patients with persistent COVID-19 symptoms. The objective of this protocol is to describe the scientific rationale in detail and to provide information about the study procedures. Methods/design: a total of 100 patients with postdischarge symptoms after COVID-19 will be randomly allocated into either a group receiving standard care (control group) or a group performing a multicomponent exercise program two times a week over a period of 6 weeks. The main hypothesis is that a 6-week multicomponent exercise program (EXER-COVID Crossover Study) will improve the immunological and inflammatory profile, physical condition, and persistent perceived symptoms (fatigue/tiredness, musculoskeletal pain, and shortness of breath) in patients with postdischarge symptoms after COVID-19. Discussion: our results will provide insights into the effects of a multicomponent exercise program on immunological parameters, physical condition, inflammatory profile, and persistent perceived symptoms in patients with postdischarge symptoms after COVID-19. Information obtained by this study will inform future guidelines on the exercise training rehabilitation of patients with postdischarge symptoms after COVID-19.
Open Access
Beneficial effects of power resistance training in patients with long COVID: the 'EXER-COVID' trial
(2025) García Alonso, Nora; Izquierdo Redín, Mikel; Ramírez Vélez, Robinson; Ciencias de la Salud; Osasun Zientziak
Esta tesis doctoral se basa en un ensayo clínico cruzado, realizado dentro del grupo E-FIT (Ejercicio Físico, Salud y Calidad de Vida) denominado 'Efectos de un programa de ejercicio físico multicomponente sobre el sistema inmune, el perfil inflamatorio, la condición física y los síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar) en sobrevivientes a la enfermedad por coronavirus (COVID-19): Un ensayo clínico cruzado'. Nuestra hipótesis de trabajo es que con la aplicación de un programa de ejercicio multicomponente de 6 semanas de duración podríamos reducir el grado de percepción de los síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar), a través de la modulación del sistema endocannabinoide, mejoraríamos el perfil inmunológico a través de la modificación gradual del sistema inmune provocado ya sea por el avance natural de la edad o por la infección de la COVID-19, incrementaríamos la condición física (capacidad funcional, fitness aeróbico y fuerza muscular) por efecto de la acción mecánica y endocrina, y reduciríamos la producción de citoquinas inflamatorias derivadas de mononucleares de sangre periférica tales como IL-1 beta, IL-6 y TNF-alfa a través del aumento de la producción y liberación de citocinas antiinflamatorias debido a la contracción del músculo esquelético, lo cual podría contribuir a reducir el proceso inflamatorio que habitualmente se instaura en la infección por la COVID-19. Los objetivos de este estudio fueron: evaluar la modificación en parámetros inmunológicos, condición física, perfil inflamatorio y cambios en síntomas percibidos persistentes (fatiga/cansancio, dolor musculoesquelético, dificultad para respirar) después de 6 semanas de ejercicio físico multicomponente y supervisado, adicionales al esquema de tratamiento médico estándar en pacientes con síntomas persistentes de la COVID-19. Antecedentes: La condición post-COVID-19 es una condición novedosa para la cual las guías recomiendan ejercicio supervisado, pero la evidencia que guía intervenciones seguras y efectivas es limitada. El objetivo de este estudio fue investigar los efectos de un programa de ejercicio adaptado (ensayo EXER-COVID) sobre la aptitud cardiorrespiratoria, la fuerza muscular, los síntomas COVID prolongados, el rendimiento cognitivo, la calidad de vida, la depresión y la angustia psicológica. Métodos: Este estudio cruzado incluyó 100 participantes con condiciones post-COVID-19 (edad media 48 años; 68% mujeres) en un único centro en España desde el 1 de marzo de 2021 hasta el 30 de septiembre de 2022. Los participantes fueron aleatorizados 1:1 a 6 semanas de entrenamiento de resistencia a la potencia muscular (PRT) seguido de 6 semanas de atención habitual (Grupo 1 [AB], n=50) o 6 semanas de atención habitual seguidas de 6 semanas de RT de potencia muscular (Grupo 2 [BA], n=50). Resultados: La intervención mejoró significativamente el pico de VO2 en 2,10 ml/kg/min [IC 95%: 1,25 a 2,94], P<0,001. Los análisis por protocolo revelaron resultados similares (2,40 ml/kg/min [IC del 95%: 1,56 a 3,25]), P<0,001. No se detectaron efectos de arrastre ni de período. Después de la PRT de potencia, la fuerza (1RM) mejoró para la prensa pectoral, la prensa bilateral de piernas, la extensión de rodillas y la prensa de espalda (P<0,001). Se encontraron disminuciones significativas en las puntuaciones de angustia psicológica (P<0,001). La intervención también mejoró la calidad de vida (P=0,041), las capacidades cognitivas (P=0,014) y el rendimiento cognitivo (P=0,036). Además, el programa de ejercicios redujo siete de los 22 síntomas de la COVID prolongada, entre ellos debilidad (RR= 0,75 [IC 95%: 0,59 a 0,95]), disnea (RR= 0,56 [IC 95%: 0,39 a 0,82]), pérdida de audición/tinnitus (RR= 0,86 [IC 95%: 0. 75 a 0,98]), cambios en el apetito (RR= 0,84 [IC 95%: 0,72 a 0,97]), pérdida de memoria (RR= 0,84 [IC 95%: 0,72 a 0,97]), estrés (RR= 0,80 [IC 95%: 0,64 a 0,99]) y apatía/depresión (RR= 0,80 [IC 95%: 0,64 a 0,99]). Conclusiones: Un programa de intervención PRT supervisado de 6 semanas mejoró de forma segura la aptitud cardiorrespiratoria, la fuerza y la salud mental en participantes con afecciones posteriores al COVID-19. Estos hallazgos proporcionan a los médicos pruebas para apoyar el ejercicio como co-terapia estándar y justifican estudios adicionales. Registro del ensayo: NCT04797871. Registrado el 15 de marzo de 2021.